Prostheses in various forms have been used for over five decades to replace dysfunctional heart valves. Each of the four heart valves in the human heart, the aortic, and mitral valves on the left side, or the pulmonary and tricuspid valves on the right side can become dysfunctional in many ways at any time, and an event (infections, structural failures such as tears or disruption of certain components as with the mitral valve chordae, or deformation because of genetic predisposition of valvular material) can disrupt the normal unidirectional flow of blood often with death as a possible outcome. For some situations there is a degree of urgency in addressing a dysfunctional valve. Historically valves have been replaced with the use of “open heart surgery” which is a highly invasive and risky procedure. These procedures can place the very young or old at high risk for procedure-induced mortality. As a result, older patients are often denied open heart surgery and are treated to make the effects more bearable during a descent until death.
The use of less risky and invasive catheter techniques to deliver stents has become widespread. This technique has been used to delivery heart valves in a like manner. Typically the catheter has a distal tip with a capsule that contains the heart valve. The distal tip is threaded through the patient's vascular system to the placement location where it replaces the function of a dysfunctional valve.
There are various ways to arrive at the site of any of the heart valves in an animal or human. The catheter containing the valved stent may be introduced into the heart in antegrade route, meaning following the flow of blood along a vessel or through the heart. Alternatively it may be introduced in retrograde manner, that is, its tip going against the flow of blood through the heart. As an illustrative example, an aortic valved stent is introduced through the femoral artery, the catheter travels retrograde to the flow of blood (against the normal flow of blood in the aorta), traveling the length of the aorta until it reaches the diseased aortic valve and the junction of aorta to the heart where it will be deposited to begin its function.
At present, most of said techniques can be used to provide a variety of options depending on the status and condition of the patient as well as to minimize longitudinal or post intervention complications, and more specifically to eliminate exposure to cardiopulmonary bypass and all its well-known untoward consequences. While the catheter-guided techniques for the aortic and pulmonary valves have been used extensively, now counting over 300,000 patients, these techniques have not yet translated into well-established mitral valve replacement techniques. The reason for this resides in the complexity of the mitral valve, that in effect is a mitral apparatus, consisting of a continuum that begins at the walls of the heart from which papillary muscles emerge that connect to a group of tendon-like filaments termed the chordae tendineae, having the appearance of parachute ropes that reach into the mitral valve leaflets' edges; said leaflets are of different shape and sizes, the anterior mitral leaflet having larger surface that connects to the atrial curtain descending from the aorta, and the posterior mitral leaflet that attaches to the outer or posterior portion of the wall of the heart. Both of these leaflets and chordal mass are contained within a not-so-continuous structure generally termed the annulus. Approach from the atrial side or the ventricular side of the valve to its annular plane poses some difficulties of navigation, not only for the approach, but for the accurate deposition of valved stents coaxially (stent lined with the central axis of the mitral valve), and the capture of the necessary leaflet and annular components to remain in place, seal the periphery between the two chambers and provide the necessary function.
Open surgical replacement has been performed for hundreds of thousands of cases of mitral valve dysfunction, be it stenosis or incompetence until it was realized that often valvular tissue in some disorders was still well preserved in whole or in part. Surgeons devised procedures to repair the malfunction in open heart procedures, a sizable percent of which were durable but only centers of excellence are able to perform the complex surgery. The number of patients affected with the condition of mitral regurgitation or valve incompetence graded in terms of its severity at higher than mild (moderate) and many graded severe is very large reaching many millions worldwide. Oern S., Liddicoat J.: Emerging Opportunities for Cardiac Surgeons within Structural Heart Disease. J Thorac and Cardiovasc Surgery: 132: 1258-1261 (2006), describe the incidence of disorders of the cardiac valves in the US population, and show that there are in the order of 2.3 million patients yearly who have dysfunctional mitral valves in various stages of the condition, with approximately 220,000 in the severe category. Of these severe patients only about 23% (48,000) receive the proper treatment for correction of the condition; a large proportion goes untreated and since the report was written over one million patients have died. Present day repair centers can only handle a few.
The translation of surgical repair techniques to catheter guided less invasive techniques began in the late 1990s in the hope of reproducing certain surgical repair techniques. It was met with many disappointments when assessing the reliability of the safety and more particularly the effectiveness of such procedures. The results in many cases are only partially satisfactory with a sizable percentage of incomplete repairs of mitral regurgitation. Although a variety of approaches have been attempted, such as trapping the mitral valve leaflets' central edges and apposing them centrally thus creating a double orifice (reproducing the surgical Alfieri edge-to-edge repair technique with catheters) to reduce mitral regurgitation is the most advanced. Others provide reduction of annular dilatation through the introduction of metallic wires through the coronary sinus vein to circumscribe the mitral valve annulus and reduce its size by constriction, but this also met with disappointing results. A few others purported to correct the condition by repair with minimally invasive procedures but results are poor at best.
In various embodiments, replacement heart valves can comprise certain components that are common to most devices for replacement of heart valves. There is often a component that will act as a support, the frame, usually referred to as the stent. Within this frame or stent, a valvular mechanism is enclosed, often having more flexibility in the case of the so called biological heart valves, as these valvular mechanisms are to undertake the restoration of the valvular function. These valvular mechanisms are comprised of sections of thin material (usually a biological membrane) that are movable under the action of the flow of blood, said sections that can be singular or be in a plurality of two or more sections is often termed the leaflets or valves. Depending on the direction of the flow of blood, these surfaces will move in the same direction, so as to open the orifice that is provided by the stent as large as it is possible without damage to the leaflet when blood flows from one chamber of the heart to the next or towards the outside the heart, and subsequently as the pumping stroke of the heart is finished, blood flow reversal instantaneously occurs and pushes the leaflets in the opposite direction closing the valve and impeding retrograde blood flow or reflux, also called regurgitation. Regurgitation clearly diminished the efficiency of the heart whose function is to maintain flow to all parts of the body.
The valves used for decades as implants for the major part consisted of the same components, namely a stent generally fabricated from polymers reinforced with wire, and a leaflet mechanism. The valved stents of the “new era” of valve therapy, are in general cylindrical tubular frames of metal, cut in such manner and shape that can be compressed to a very small diameter, close to the original diameter of the tube while including the tissue valvular mechanism, such that the whole valve can be threaded through the vasculature with the aid of catheters, in the smaller possible profile to minimize or totally avoid damage to the bioprosthesis and the patients vascular route to the valve in the heart that is to be “replaced”. These metal stents are generally made of rust-free very pure stainless steels (alloys of iron and other metals) that require a liquid filled balloon under pressure to expand said stents to their final or nominal diameter, but often in their final expanded diameter are still subject to the pressures the tissue may apply and be deformed inwardly. Other metal alloys used are the so-called shape memory metals that can be compressed to the small diameters desired at specified low temperature ranges and on their own, because of their molecular composition, will expand under the second conditions of temperature (i.e. body temperature) to their original pre-compression nominal diameter, that is, the framework has temperature shape-memory. The stents, in effect the valve, in the “new era” of heart valve therapy are conformed to meet a specified requirement to perform the needed function. This very stringent requirement is the ability to remain in the intended position, or the landing area. That is, it will not dislocate or migrate such that it is in effect anchored for the duration of its use as that patient's valve function is needed. In addition the valved stent must seal the periphery to avoid leakages that can be very damaging to the blood and the health of the patient, and otherwise may require revision or surgery for correction of those events.
The use of stents in aortic valve replacement therapy is mostly for aortic stenosis, a disease that often occurs because of the pathological mineralization of the tissue that constitutes the aortic heart valve. Leaflets of the aortic valve become thickened and calcium deposits by diffusion from the blood plasma within the leaflet tissue and at times on the surface of the tissue, hardening the leaflets and their mobility to the point that they practically close by narrowing (stenosis) the orifice leading from the left ventricle to the aorta so that blood cannot follow a normal flow. The ventricle pumping overexerts its muscle which becomes thickened trying to pump blood through a smaller orifice of the aortic valve and slowly its function decays. The body is deprived of blood and organ conditions and quality of life decreases rapidly. Catheter-guided implanted valved stents that are used to correct the disease rely purely on the force exerted by the stent on the calcified rocky leaflets. These stents are cylindrical in the neighborhood of the valve and the walls of that cylinder exert the pressure to keep the valved stent in the area of the native aortic valve by interference fit. This pressure will be exerted by dilation of the stainless steel valved stent with a balloon, or by the temperature shape memory force of the expanded stent. It is an entirely different set of conditions that are present in the case of mitral valve regurgitation.
Mitral regurgitation (MR) can be caused by many conditions, some are more amenable to the use of valved stents. One form of condition results from changes in the shape and size of the heart, by dilatation of both heart and mitral valve annulus (dilated cardiomyopathy, DCM). This condition alters the valvular function and as such is termed functional mitral regurgitation. It is a vicious cycle, when myocardial (heart muscle) damage results in left ventricle dilation which in turns leads to apical dislodgement of the papillary muscles. These muscles lead to annular dilatation and these two combine to produce mitral regurgitation causing left ventricle overload that results in left ventricle dilatation and the cycle begins again. The annulus and the mitral valve and the atrial curtain has lost its ability to maintain the size of the mitral valve orifice. Dilatation can expand this orifice to almost double its size in extreme cases and leaflets are far apart at a time in the heart cycle (systole) when they should be in apposition and closing the valve orifice to impede reflux into the chamber (atrium) from which fractions of a second previously blood flowed into the ventricle. The annulus is soft and pliable and somewhat less pliable in parts, and exerting pressure radially on it as aortic stents would only lead to more expansion and aggravate the condition.
There are no prosthetic mitral valve devices at present that have been fully developed and commercialized for placement in a dysfunctional mitral valve or replacement of the native mitral valve function by percutaneous means or catheter-guided means. Accordingly, it must be reiterated that there is a very strong need for improved designs of valved stents, and devices of delivery that will result in improved embodiments to replace the function of mitral heart valves, and tricuspid valves for which there are none fully developed at present. Said embodiments must enable the precise delivery, deployment and deposition of valved stents into the atrioventricular annuli and their engagement with minimal complications and restoration of function as near as possible to that of normal healthy human valves. Said embodiments must also prevent the development of peripheric valvular leaks (PVL), that is, the development of leaks between the implanted valved stent and the native valular tissue to which the stent must conform very closely.